Risk	Disease/Therapy Examples	Bacterial	Fungal	Viral
Low	• Standard chemo • Most solid tumors • Anticipated neutropenia <7 days	None	None	None unless prior HSV episode
Intermediate	• AutoHCT • Lymphoma • Multiple myeloma • CLL • Purine analogs (fludarabine, clofarabine, nelarabine, cladribine) • Neutropenia 7–10 days • CAR T-cell therapy	Consider FQ during neutropenia	Consider during neutropenia/mucositis; consider PJP ppx	During neutropenia, longer per risk
High	• AlloHCT (incl. cord blood) • Acute leukemia induction/ consolidation/maintenance • Alemtuzumab • Moderate-severe GVHD • Neutropenia >10 days	Consider FQ during neutropenia	Consider during neutropenia; consider PJP ppx	During neutropenia + longer; duration tied to immune reconstitution

Bacterial Prophylaxis Criteria (NCCN v1.2026, INF-1)

Bottom line: Risk stratification drives everything. NCCN does not gate bacterial prophylaxis on a single criterion — it uses an Overall Infection Risk category (Low/Intermediate/High) built from: underlying malignancy, remission status, anticipated duration of neutropenia, prior chemo exposure, CMV serostatus, and intensity of immunosuppressive therapy.

Risk	Disease/Therapy Examples
Low	• Standard chemo • Most solid tumors • Anticipated neutropenia <7 days
Intermediate	• AutoHCT • Lymphoma • Multiple myeloma • CLL • Purine analogs (fludarabine, clofarabine, nelarabine, cladribine) • Neutropenia 7–10 days • CAR T-cell therapy
High	• AlloHCT (incl. cord blood) • Acute leukemia induction/ consolidation/maintenance • Alemtuzumab • Moderate-severe GVHD • Neutropenia >10 days

Agent Selection

Preference	Agent	Notes
Preferred	Levofloxacin 500–750 mg PO/IV daily	Best Gram-positive coverage among fluoroquinolones for this indication; data-supported (Bucaneve NEJM 2005; Cullen NEJM 2005)
Alternative	Ciprofloxacin	No anaerobic activity; weaker Gram-positive coverage; avoid as empiric FN therapy if pt already on FQ prophylaxis
If FQ-intolerant	TMP/SMX or oral 3rd-gen cephalosporin	Category 2B

Explicit Exclusion

Antibacterial prophylaxis is NOT recommended for low-risk patients, and in patients with neutropenia <7 days who are not on immunosuppressive regimens (e.g., systemic corticosteroids), the Panel suggests no prophylaxis at all — regardless of malignancy type.

Clinical Pearls

1. Duration is the real lever, not the drug class itself. The >7-day (intermediate) vs >10-day (high-risk) cutoffs are what push you from “consider” to stronger consideration — always anchor your assessment to anticipated ANC nadir duration, not just diagnosis.
2. Levofloxacin > ciprofloxacin for prophylaxis specifically because of superior Gram-positive activity — relevant since viridans group strep bacteremia is a real threat in profound mucositis/neutropenia.
3. The NEJM trials (Bucaneve 2005, Cullen 2005) showed FQ prophylaxis reduces fever and bacteremia, not mortality. Don’t oversell the mortality benefit on rounds — it’s a fever/documented infection reduction benefit, reinforced more recently by the Gafter-Gvili meta-analysis (2005) showing a mortality benefit specifically in afebrile neutropenic patients as a pooled population, not necessarily replicated per-trial.

Critical Pharmacist Watchouts

• The “preclusion trap”: If a patient is already on FQ prophylaxis and develops neutropenic fever, you cannot use oral fluoroquinolone-based outpatient empirical therapy for that same episode — this changes your FN risk/disposition recommendation in real time during tumor board or rounds.
• MDRO stewardship tension: FQ prophylaxis carries real risk of selecting fluoroquinolone-resistant Gram-negatives and is linked to C. diff and MRSA risk — flag this explicitly when prophylaxis is being considered in patients with prior resistant organism colonisation/infection history.
• Solid tumor/autoHCT nuance: Per the Gafter-Gvili analysis, the vancomycin-containing prophylactic regimen used in some autoHCT trials is not NCCN/IDSA-endorsed — don’t let a study’s regimen get conflated with current guideline-recommended prophylaxis.
• TMP/SMX as an FQ alternative carries interaction baggage — watch methotrexate co-administration and monitor renal function, myelosuppression, hepatotoxicity, and hyperkalaemia.
• This entire pathway is Category 2A unless otherwise noted — the FQ-intolerant alternative (TMP/SMX or oral 3rd-gen cephalosporin) is Category 2B, a lower-consensus recommendation worth flagging in documentation/tumor board discussion.

HSV/VZV Prophylaxis Criteria (NCCN v1.2026, INF-3, FEV-C, INF-A)

Risk-Stratified Prophylaxis Algorithm (INF-3)

Risk categories are determined by underlying malignancy, remission status, duration of neutropenia, prior chemo exposure, CMV serostatus, and intensity of immunosuppressive therapy (IST) (footnote a).

Risk Tier	Disease/Therapy Triggers	HSV Prophylaxis	VZV Prophylaxis
Low	Standard chemo regimens for solid tumors	None, unless prior HSV episode — if so, treat during active therapy/neutropenia only	None
Intermediate	• AutoHCT • Lymphoma • Multiple myeloma • CLL • Purine analogs (e.g., fludarabine) • CAR T-cell therapy	Consider during active therapy ± longer depending on immunosuppression degree	Consider for ≥6–12 months post-autoHCT or post-CAR T
High	Acute leukemia (induction/consolidation)	During active therapy including neutropenia	—
High	Proteasome inhibitors	—	During active therapy including neutropenia
High	Alemtuzumab	Minimum 2 months post-alemtuzumab AND until CD4 ≥200 cells/mcL	Same dual criterion applies
High	AlloHCT	During neutropenia	≥1 year post-transplant
High	GVHD requiring significant escalation of IST	Extend duration	Extend duration

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Antiviral Agents: Exact Dosing (FEV-C)

Agent	Prophylaxis Dose	Treatment Dose	Spectrum	Comments/Cautions
Acyclovir	HSV: 400–800 mg PO BID; VZV (allo-HCT): 400–800 mg PO BID; Post-VZV exposure ppx: 800 mg PO 5×/day	• Mucocutaneous HSV: 5 mg/kg IV q8h ×7–10d • Single dermatomal VZV: 800 mg PO 5×/day OR 10 mg/kg IV q8h ×7–10d • Disseminated HSV/VZV or encephalitis: 10 mg/kg IV q8h	HSV, VZV	Hydration to avoid crystal nephropathy at high dose; dosed on ideal body weight; renal-adjusted
Valacyclovir (preferred oral agent for both HSV & VZV)	HSV or VZV: 500 mg PO BID — preferred over oral acyclovir for VZV	HSV: 1 g PO BID VZV: 1 g PO TID Preferred over oral acyclovir for both	HSV, VZV	Renal-adjusted
Famciclovir	HSV or VZV: 250 mg PO BID	HSV: 250 mg PO TID VZV: 500 mg PO TID	HSV, VZV	No data for oncology-specific prophylaxis — third-line by default
Foscarnet	—	Acyclovir-resistant HSV: 40 mg/kg IV q8–12h ×7–10 days	HSV, VZV (resistant strains)	Reserved for acyclovir resistance only
Ganciclovir	—	CMV-focused (5 mg/kg q12h induction); also active against HSV/VZV	CMV, HSV, VZV	May cause bone marrow suppression
Valganciclovir	—	CMV-focused (900 mg PO BID induction); also active against HSV/VZV	CMV, HSV, VZV	May cause bone marrow suppression
Cidofovir	—	5 mg/kg IV weekly ×2 wks, then 5 mg/kg q2wks with probenecid + IV hydration	CMV, HSV, VZV, adenovirus	Nephrotoxicity (probenecid required), ocular toxicity, bone marrow toxicity

Immune/Targeted Therapy Triggers for HSV/VZV Prophylaxis (INF-A)

Drug Class	Agent(s)	HSV/VZV Recommendation Strength
Anti-CD20	Rituximab, obinutuzumab	Consider prophylaxis
Anti-CD38	Daratumumab, isatuximab	Recommend prophylaxis
Anti-CD52	Alemtuzumab	Recommend prophylaxis
Anti-CD319 (SLAMF7)	Elotuzumab	Recommend prophylaxis
Anti-CD30	Brentuximab vedotin	Consider prophylaxis
Anti-CD79b	Polatuzumab vedotin	Consider, based on concomitant immunosuppression
Anti-CD19	Tafasitamab	Consider prophylaxis
CCR4-targeted	Mogamulizumab	Recommend prophylaxis
GPRC5D/CD3 bispecific	Talquetamab	Recommend prophylaxis
BCMA/CD3 bispecific	Teclistamab, elranatamab	Recommend prophylaxis
CD19/CD3 bispecific	Blinatumomab	Consider prophylaxis
CD20/CD3 bispecific	Epcoritamab, glofitamab, mosunetuzumab	Recommend prophylaxis
DLL3/CD3 bispecific	Tarlatamab	Consider VZV prophylaxis

Cross-Reference Rule (HSV/VZV vs. CMV Prophylaxis)

• Patients on ganciclovir or foscarnet for CMV prophylaxis do not need separate HSV prophylaxis (both agents are HSV-active).
• Patients on letermovir for CMV prophylaxis DO require separate HSV prophylaxis — letermovir has no HSV/VZV activity. This is a critical, frequently-missed order-verification point.

Clinical Pearls

1. Donor-OR-recipient rule (HCT): prophylaxis triggers off either party’s seropositivity — don’t rely solely on the recipient’s serology when reviewing transplant orders.
2. Dual-criterion stop point for alemtuzumab: ppx continues until both 2 months have elapsed and CD4 ≥200 — whichever takes longer.
3. Valacyclovir is guideline-preferred over acyclovir for both HSV and VZV treatment AND VZV prophylaxis — this is an explicit 2026 update, useful when reconciling order sets still defaulting to acyclovir.
4. Famciclovir has zero oncology-prophylaxis evidence base per NCCN — appropriate only as an alternative when acyclovir/valacyclovir are contraindicated.
5. Foscarnet is exclusively a resistance-rescue agent for HSV — verify acyclovir-resistance documentation (clinical or genotypic) before allowing foscarnet orders to proceed unchallenged.

Pharmacist Watchouts

• On chemo order verification: confirm letermovir + HSV ppx co-ordering — this gap is easy to miss since both are “antiviral” and look redundant at a glance.
• On tumor board for any bispecific/CAR-T regimen: confirm HSV/VZV ppx is reflexively ordered — many newer T-cell engagers (teclistamab, talquetamab, epcoritamab) carry “recommend” (not just “consider”) strength.
• Acyclovir IV dosing — verify ideal body weight is used, not actual, especially in obese patients; recalculate independently rather than trusting order-entry defaults.
• Pediatric patients: do not extrapolate adult VZV ppx duration rules — pediatric VZV ppx is reserved for recurrent/myelosuppression-associated zoster, not routine seropositivity.

PJP Prophylaxis Criteria (NCCN v1.2026; INF-6, INF-A, MS-29)

High Risk for Pneumocystis jirovecii (INF-6)

PJP prophylaxis risk in two tiers: definite indications and “consider” (category 2B) indications. Duration is immune-recovery-anchored, not calendar-fixed, for most categories.

Allogeneic HCT (including cord blood) — Category 1

• Duration: For at least 6 months and while receiving IST (whichever is longer)
• Pearl: This is the only indication tied to two conditions (time AND immune status) — a patient still on tacrolimus/sirolimus for GVHD at month 9 still needs PJP ppx even though the “6 month” clock has passed. Don’t let a 6-month auto-stop order lapse if IST is ongoing.
• Watchout: On tumor board/rounds, cross-check the IST taper schedule before endorsing d/c of PJP prophylaxis — pharmacy is often the only team member tracking both concurrently.

Cellular immunotherapies (CAR T-cell, TCR, TIL therapy)

• Duration: For at least 6 months and while receiving IST (same structure as alloHCT)
• Pearl: This is distinct from the older literature that only flagged CAR T neutropenia/ICAHT risk — NCCN now explicitly puts CAR T PJP risk on par with alloHCT in duration logic.
• Watchout: CRS/ICANS management often introduces high-dose corticosteroids or tocilizumab mid-course — this extends the IST clock and thus PJP ppx duration. Flag this at every CAR T toxicity huddle.

ALL (Acute Lymphoblastic Leukemia) — Category 1

• Duration: Throughout anti-leukemic therapy (i.e., induction → consolidation → maintenance, no gap)
• Pearl: ALL is the only leukemia subtype given its own category 1 designation independent of neutropenia duration — this reflects the prolonged, multi-year nature of ALL maintenance (often with concurrent corticosteroid pulses).
• Watchout: Vincristine + TMP/SMX has no major interaction, but methotrexate + TMP/SMX does — trimethoprim inhibits dihydrofolate reductase and competes with renal tubular MTX secretion, raising myelosuppression risk. This exact interaction is called out in NCCN’s FEV-A dosing table (“Interactions with methotrexate”). This is a critical order-verification point in ALL maintenance regimens using intermittent MTX.

Alemtuzumab

• Duration: Minimum 2 months, and CD4 count >200 cells/mcL used as an adjunct in decision-making
• Pearl: Alemtuzumab causes the most profound and prolonged T-cell depletion of any agent on this list (targets CD52 on both T and B cells) — hence why CD4 recovery, not a fixed calendar date, drives the stop decision.
• Watchout: Don’t rely on absolute neutrophil count recovery as a surrogate for immune reconstitution in alemtuzumab patients — ANC normalizes long before CD4 does. Order CD4 counts proactively; don’t wait for ID/heme to ask.

Consider (Category 2B) — Purine analog therapy & other T-cell–depleting agents

(fludarabine, clofarabine, nelarabine, cladribine [2-CdA] per INF-1 examples)

• Duration: 6–12 months, and CD4 count >200 cells/mcL used as an adjunct in decision-making
• Pearl: This is category 2B — meaning lower-level evidence/lesser panel consensus, not absent risk. Purine analogs cause profound, dose-cumulative lymphocytopenia (this is the exact mechanism relevant to the cladribine/hairy cell leukemia scenario we discussed previously).
• Watchout: 2B still means “should generally be offered,” per NCCN category definitions — it does not mean optional in practice. Don’t let the lower category grade become an excuse to skip prophylaxis at chemo order verification.

Consider (Category 2B) — Autologous HCT

• Duration: 3–6 months post-transplant
• Pearl: AutoHCT carries meaningfully lower PJP risk than alloHCT because there’s no GVHD/IST superimposed on the transplant-related immunosuppression — this is why the duration is shorter and the category grade lower.
• Watchout: If a patient converts from planned autoHCT to a tandem or later allo, immediately re-stratify to the alloHCT (category 1, IST-linked) duration rules — don’t leave them on the shorter autoHCT clock by default.

Additional PJP Prophylaxis Triggers (MS-29 narrative text + INF-A, outside the INF-6 table itself)

Corticosteroids — prednisone-equivalent ≥20 mg/day for ≥4 weeks

• Category: Category 2A (“consider”); footnote “z” specifically ties risk to daily dose and duration
• Duration: At least through active treatment
• Pearl: Risk is a dose × duration function, not a threshold event — a patient on dexamethasone 4mg BID (~10mg prednisone-equivalent) chronically for CNS mets may cumulatively cross this threshold well before anyone notices, especially with pulsed regimens (VAD, hyper-CVAD, RCHOP with steroid tapers).
• Watchout: This is the single most commonly missed PJP indication on chemo order review because no one is doing a formal steroid-equivalent calculation across regimens/supportive care orders. Build steroid-day tracking into your verification workflow, not just at initiation but longitudinally.

Temozolomide ± radiation therapy

• Duration: Continue until recovery from lymphocytopenia (footnote “aa”)
• Pearl: This is a neuro-oncology-specific indication frequently missed by non-neuro-onc pharmacists — TMZ + concurrent RT (Stupp protocol) causes a well-documented, delayed CD4 lymphopenia nadir that can occur weeks after RT completion, not during it.
• Watchout: Don’t anchor PJP ppx duration to the TMZ treatment calendar alone — track absolute lymphocyte count (ALC) trend, since lymphopenia frequently outlasts active dosing.

Select monoclonal antibodies / targeted agents (INF-A tables 1 & 2)

Per the agent-specific INF-A tables, PJP is flagged as a concern with a “consider” or “recommend” prophylaxis note for: CD20 (rituximab, obinutuzumab), CD30 (brentuximab vedotin), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab, isatuximab), CD52 (alemtuzumab — recommend if CD4 <200), CD79b (polatuzumab vedotin), PI3K inhibitors (idelalisib, duvelisib, copanlisib), mTOR inhibitors (everolimus, temsirolimus, sirolimus — if additional risk factors), and bispecifics (talquetamab, mogamulizumab).

• Pearl — alpelisib exception: NCCN explicitly states “Alpelisib has not been associated with PJP or CMV risks,” distinguishing it from idelalisib/duvelisib despite the shared PI3K-inhibitor class. Don’t class-extrapolate PJP risk across all PI3K inhibitors — isoform specificity matters (alpelisib is PI3Kα-selective vs. the pan-class/δ-isoform agents).
• Watchout: These are almost always layered on top of an existing chemo backbone (e.g., rituximab + bendamustine, daratumumab + dex) — the “concomitant therapy” risk-stacking language in NCCN (“especially if concomitant therapy further increases PJP risk”) means your job at order verification is to sum the regimen’s total immunosuppressive burden, not evaluate each drug in isolation.

Drug Selection & Dosing (FEV-A dosing table, verbatim regimen structure)

TMP/SMX — preferred, Category 1

• Prophylaxis: Single-strength daily or double-strength 3x/week
• Treatment (active PJP): 8–15 mg/kg/day (based on trimethoprim component), divided q6–8h
• Spectrum bonus: Also covers Toxoplasma gondii and Nocardia — relevant in your severely T-cell-depleted patients (alemtuzumab, purine analogs) who are simultaneously at risk for these co-infections
• Monitoring: Renal insufficiency, myelosuppression, hepatotoxicity, hyperkalemia
• Interaction: Methotrexate (noted above)

If TMP/SMX intolerant:

1. Desensitization — first-line consideration before switching, specifically because you lose the Nocardia/Toxoplasma coverage with alternatives
2. Atovaquone — comparable efficacy to dapsone in HIV literature; effective pediatric ALL data
3. Dapsone — check G6PD prior to initiation (hemolysis risk in deficient patients); monitor for methemoglobinemia
4. Pentamidine (aerosolized or IV) — third-line alternative

Clinical Pearls

1. Two questions to ask for every case, every time: (1) Does this regimen meet an INF-6 category 1/2B trigger? (2) Does the cumulative steroid or T-cell-depleting burden cross the “consider” thresholds even if no single drug does? Missing #2 is the more common real-world gap.
2. Duration logic is binary across the whole table: either it’s time-anchored (ALL = throughout therapy; alemtuzumab/purine analogs/autoHCT = fixed months) or immune-marker-anchored (alloHCT/CAR T = IST status; TMZ = lymphopenia recovery; alemtuzumab/purine analogs also incorporate CD4). Always identify which logic applies before recommending a stop date.
3. Category grade (1 vs. 2A vs. 2B) reflects evidence strength, not clinical importance — don’t let a 2B grade lower your threshold to recommend prophylaxis at tumor board.

Pharmacist Watchout

• ☐ Verify a documented CD4 count exists (not just ANC) before endorsing d/c of PJP ppx in alemtuzumab/purine analog/CAR T-cell patients
• ☐ Calculate cumulative steroid-day burden across the entire regimen (chemo + antiemetic + GVHD steroids), not just the “chemotherapy” order
• ☐ Confirm G6PD status is on chart before dapsone is dispensed
• ☐ Flag MTX + TMP/SMX co-administration in ALL maintenance for enhanced myelosuppression monitoring
• ☐ For CAR T patients, re-assess PJP ppx duration at every CRS/ICANS steroid escalation, not just at baseline order entry
• ☐ Don’t extrapolate PI3K-inhibitor PJP risk to alpelisib

Fungal Prophylaxis Criteria (NCCN v1.2026, INF-1)

PROPHYLAXIS — Risk Stratification Trigger (INF-1)

Risk Tier	Disease/Therapy Trigger	Fungal Prophylaxis Directive
Low	Standard solid-tumor chemo; anticipated neutropenia <7 days	None
Intermediate	Autologous HCT; lymphoma/myeloma/CLL (heterogeneous — depends on regimen intensity); purine analogs (fludarabine, clofarabine, nelarabine, cladribine); anticipated neutropenia 7–10 days; CAR T	Consider prophylaxis during neutropenia + for anticipated mucositis; consider PJP ppx
High	Allogeneic HCT (incl. cord blood); acute leukemia induction/consolidation; alemtuzumab; moderate-severe GVHD; anticipated neutropenia >10 days	Consider prophylaxis during neutropenia; consider PJP ppx

Disease-Specific Antifungal Agent Selection (INF-2)

Disease/Therapy	Preferred (Cat 1 where noted)	Alternatives (Cat 2B)	Duration
ALL	Fluconazole or echinocandin	Amphotericin B products	Until neutropenia resolves
MDS/AML (neutropenic)	Posaconazole (Cat 1)	Voriconazole, isavuconazole, echinocandin, amphotericin B, fluconazole (if no mold activity needed)	Until neutropenia resolves
Autologous HCT + mucositis	Fluconazole or echinocandin (both Cat 1)	—	Until neutropenia resolves
Autologous HCT, no mucositis	No prophylaxis (Cat 2B)	—	N/A
Allogeneic HCT (neutropenic)	Fluconazole or echinocandin (both Cat 1)	Voriconazole, posaconazole, isavuconazole, amphotericin B	Continue through neutropenia (some centers to day 75)
Significant acute GVHD (Gr 3/4) on intensive IST	Posaconazole (Cat 1) — based on Ullmann NEJM 2007 RCT (severe GVHD requiring intensive IST)	Voriconazole, echinocandin, amphotericin B, isavuconazole	Until significant GVHD resolves
CAR T-cell therapy	Mold-active prophylaxis only if additional risk factors (prolonged neutropenia, prior allo-HCT, augmented IST for CRS/ICANS)	—	Depends on duration of risk factor

Pharmacist watchout: Posaconazole has not been studied as prophylaxis during the neutropenic conditioning phase of allogeneic HCT — safety in that specific window is unestablished; tailor with ID input.

Treatment of Documented Invasive Fungal Disease

Invasive Candidiasis/Candidemia — IDSA + NCCN concordant:

• Echinocandin = preferred initial therapy in most neutropenic and non-neutropenic patients (NCCN Cat 1, agreeing with IDSA)
• C. krusei → intrinsically fluconazole-resistant
• C. glabrata → variable azole susceptibility → echinocandin preferred
• C. parapsilosis → reduced echinocandin susceptibility → fluconazole preferred
• C. auris → may resist both fluconazole and echinocandins
• Amphotericin B not routine — reserve for meningitis/endocarditis or refractory cases
• Echinocandins have poor CNS, urinary, ocular penetration — do not use for candidiasis at these sites

Invasive Aspergillosis — Voriconazole monotherapy = Cat 1 primary therapy (Herbrecht NEJM 2002: 53% vs 32% response, improved 12-wk survival vs amphotericin B). Isavuconazole = non-inferior alternative (SECURE trial), better tolerated.

Mucormycosis — No agent has Cat 1 RCT data. Amphotericin B (lipid formulation, ~5 mg/kg/d) + early aggressive surgical debridement is the backbone. Isavuconazole (FDA-approved for mucormycosis) or posaconazole (not FDA-approved for this indication) for refractory/intolerant cases or step-down maintenance.

Empiric/Site-Directed Triggers

• Empiric antifungal in persistent neutropenic fever: standard window = 4–7 days unresponsive to broad-spectrum antibiotics; high-risk patients (neutropenia >10 days, allo-HCT, high-dose corticosteroids) → add at day 4 unless already on mold-active prophylaxis.
• Oral/oropharyngeal candidiasis (mucositis findings): fluconazole first-line → voriconazole/posaconazole/echinocandin if fluconazole-refractory.
• Sinus/nasal findings (periorbital cellulitis, nasal ulceration, unilateral eye tearing) + suspicious CT/MRI: add lipid amphotericin B empirically to cover Aspergillus/Mucorales pending biopsy in high-risk patients.

Clinical Pearls

1. Posaconazole’s Cat 1 status is indication-specific — it only earns Cat 1 in AML/MDS prophylaxis (Cornely NEJM 2007) and severe GVHD on intensive IST (Ullmann NEJM 2007). Don’t extrapolate Cat 1 confidence to other settings.
2. Echinocandins ≠ universal fungal coverage — no reliable CNS/eye/urinary penetration, and no reliable Mucorales activity. A “fungal coverage” order set defaulting to micafungin will miss mucormycosis and CNS candidiasis.
3. Azole-vinca/PI/TKI interaction rule: mold-active azoles (itra-, vori-, posaconazole) must be held several days before and not restarted until clearance of interacting cancer drugs — this is explicit NCCN Panel guidance, not just general PK reasoning.
4. Voriconazole TDM target: trough ≥1–2 mcg/mL at one week — sub-therapeutic levels correlate with progression; supratherapeutic with toxicity (neurotoxicity, hepatotoxicity).

Critical Pharmacist Watchouts

• Trigger phrase to listen for: “persistent fever day 4–5 on broad-spectrum antibiotics” in a high-risk patient (neutropenia >10d, allo-HCT, high-dose steroids) → you should be prompting empiric antifungal now, not waiting to day 7-10.
• Voriconazole given for AML prophylaxis history → mucormycosis index of suspicion goes UP — breakthrough mold infections under voriconazole prophylaxis carry a documented mucormycosis association.
• Don’t let the team confuse “Cat 1” for “only option” — many Cat 2B options exist when Cat 1 agents are contraindicated (e.g., voriconazole/itraconazole avoided for QTc or drug-interaction reasons → isavuconazole or echinocandin substituted).
• For candidemia, always ask “what species, what’s the susceptibility, any recent azole exposure?” before de-escalating echinocandin → fluconazole, per IDSA stepping-down criteria the NCCN panel endorses.

CMV Prophylaxis Criteria (NCCN v1.2026, INF-4)

CMV Prevention (Surveillance-Based, not classic prophylaxis except letermovir)

High risk for CMV:

• AlloHCT recipients (CMV IgG+)
• GVHD requiring therapy
• Alemtuzumab (surveillance ≥2 months post-therapy)

Surveillance: Weekly CMV PCR (treatment threshold varies by institution).

Letermovir — primary prophylaxis for CMV-seropositive (R+) allogeneic HCT recipients: 480 mg PO/IV daily (240 mg if on cyclosporine).